The invention relates to a single-component or multiple-component polyelectrolyte cement containing at least two reaction partners, (a) a metal-cation-releasing compound and (b) one or more polyelectrolytes capable of being converted into a solid state, wherein at least one of the polyelectrolytes is at least partially water soluble, and wherein at least one part of reaction partner (a) and/or (b) is coated with an organic surface coating agent. Moreover, the invention relates to a granulate obtained from at least one part of the formulation constituents of the polyelectrolyte cement present in solid form, wherein, in the context of an autogenous granulation process, at least one part of reaction partner (b) serves as the essential granulation agent, and the granulate disintegrates back to the primary grain on contact with the liquid formulation constituents.
Furthermore, the invention relates to processes for production of the granulate and the use of the polyelectrolyte cement as a dental material.
In the sense of the present invention, polyelectrolytes are understood to be polymers with ionically dissociable groups, which may be a component or a substituent of the polymer chain and of which the number is so great that the polymers are at least partially water soluble at least in their partially dissociated form. In the sense of the present invention, polyelectrolyte cements are understood to be materials which contain a polyelectrolyte. In particular, these polyelectrolytes should be able to react with a metal-ion-releasing compound in the context of a chelate-forming reaction, particularly preferably, an acid-base reaction/neutralization reaction. This reaction is described as a curing reaction or simply as curing. A polymerization reaction may also take place alongside this curing, if polymerizable compounds are added together with initiators suitable for the polymerization of these compounds.
Polyelectrolyte cements of this kind are obtained, for example, through the reaction of a polyalkenoic acid, in particular a polyacrylic acid, with zinc oxide or a metal-cation-releasing, so-called basic glass powder in the presence of water. These cements have been known since 1967 as polycarboxylic cements [D. C. Smith, Biomaterials 19, 467-478 (1998)] and since 1969 as (conventional) glass-ionomer cements (glass-polyalkenoate cements, GIC) [A. D. Wilson, B. E. Kent, DE 20 61 513]. Polyelectrolyte cements which contain additional polymerizable compounds and suitable initiators are, for example, synthetically modified glass-ionomer cements (see e.g. R. Mathis, I. L. Ferracane, J. Dent. Res. 66, 113 (Abstract 51) (1987)] or compomers [see e.g. EP 219 058].
The above named polyelectrolyte cements can be formulated as two-component paste-paste systems and single-component paste systems. Normally, however, the above-named polyelectrolyte cements are formulated as powder-liquid systems. In this context, the polyelectrolyte may be either in the liquid, or it may be mixed with the powder as a solid. Mixed forms, in which parts of the polyelectrolyte are contained in the powder and parts in the liquid, are also known [see, for example, GB-A-17880-72, DE-A-2319715]. Solid mixtures, in which at least one part of the polyelectrolyte is present alongside a metal-cation-releasing compound, are defined as xe2x80x9cdry powder mixturesxe2x80x9d.
Addition of polyelectrolytes to the powder as a solid is advantageous, for example, if additional processing time is to be gained by the dissolution of the polyelectrolyte or if the complete amount of polyelectrolyte in the solution leads to a high, and therefore no longer suitable viscosity and workability.
One disadvantage of the dry powder mixture is that in the presence of moisture, e.g. from atmospheric humidity during the storage of the product up to the time of use, a reaction takes place between the two reaction partners, i.e. the metal-cation-releasing compound and the polyelectrolyte, which slows down the curing of the cement. This means that a reliable use of the polyelectrolyte cement is no longer guaranteed, because the curing of the material increases in dependence upon the duration of storage.
This plays an important role, in particular with the hand-mixed variants of these polyelectrolyte cements, because these products are conceived for the cost-conscious user in such a manner that several applications can be implemented with the packaged material. Accordingly, the dry powder mixture is provided in small glass containers which allow access to atmospheric moisture every time the material is removed, which slows down the curing. Moreover, in time, it becomes more difficult to mix the cement because, as a result of the reaction occurring at the surface between the metal-cation-releasing compound and the polyelectrolyte in the presence of atmospheric humidity, agglomerates of increased solidity may be formed and can only be broken down with an increased input of energy during mixing.
It is possible to achieve stable curing throughout the storage period by preventing the access of moisture to the dry powder mixture. This can only be realized through more elaborate packaging: for example, polyelectrolyte cements of this kind which are offered in a mixing capsule specially developed for single application, are blister-packed in aluminium foil possibly with an additional dessicant pad. Indeed, this measure does have the desired stabilizing effect on curing, but is associated with significantly increased cost of manufacture which is therefore transferred to the consumer. Moreover, with increasing awareness of environmental matters, the consumer""s acceptance of an elaborately packaged product is constantly declining.
Also, particular steps must be taken during production and packaging of the dry powder mixture in order to minimize contact with atmospheric moisture as much as possible, otherwise initial damage to the dry powder mixture may occur and this may cause difficulties with the packaging of the dry powder mixture which leads to increased expenditure on maintenance.
Another option for protecting substances essentially from environmental influences is to provide the substances to be protected with a coating.
Organic coating compounds used in the production of tablets [H. P. Fiedler, Lexicon der Hilfsstoffe fxc3xcr Pharmazie, Kosmetik und angrenzende Gebiete (Dictionary of excipients for pharmaceutical, cosmetics and associated areas) Editio Cantor Verlag Aulendorf, 4th edition, 1996, pages 1498-1500] are known in the pharmaceutical industry. Depending on the area of use of the tablet, these coating compounds may be soluble in acid (solubility in the stomach), soluble in alkali (solubility in the intestine) or soluble in water. Typical representatives of these very widely used tablet coatings are the Eudragit(copyright) types manufactured by Rxc3x6hm. Eudragit(copyright) L (acid-resistant) is an acid-functional polymer, while Eudragit(copyright) E (acid soluble) provides amino groups [H. P. Fiedler, Lexicon der Hilfsstoffe fxc3xcr Pharmazie, Kosmetik und angrenzende Gebiete (Dictionary of excipients for pharmaceutical, cosmetics and associated areas) Editio Cantor Verlag Aulendorf, 4th edition, 1996, pages 596-598]. The product Copolymer 845 manufactured by ISP, which provides tertiary amino and pyrrolidon groups, is also amino-functional, however, water soluble. Coating compounds based on cellulose derivatives (such as OPADRY(copyright) II, manufactured by Colorcon, or Sepifilm, manufactured by Seppic) are also known. Copolymers, which also contain polysaccharides, such as e.g. Surelease (by Colorcon) are also used for this purpose (see product catalogues of the individual companies).
The manufacturers provide recommendations regarding the film thickness required to achieve resistance to moisture with these coating compounds. For example, Rxc3x6hm recommends film thicknesses of approximately 10 xcexcm for the production of moisture-resistant tablet coatings; this corresponds to around one milligram of coating compound per cm2 (Eudragit(copyright) product catalogue by Rxc3x6hm). To achieve the recommended film thickness on the finely ground constituents of the powder in a polyelectrolyte cement (specific surface of approximately 3 m2 per gram), this would have to be coated with approximately 30 grams of coating compound per gram of powder.
This represents a substantial intervention into the composition of the polyelectrolyte cement. It must be regarded as particularly important in this context that the materials named for surface coating are non-reactive additives with reference to a polyelectrolyte cement reaction. Even earlier experiments have repeatedly shown that in the case of polyelectrolyte cements, non-reactive additives generally lead to a significant deterioration of properties even in concentrations of a few percent; this applies in particular with reference to mechanical values such as compression strength or bending strength.
DE 3610844 and DE 3610845 describe surface coating agents for dental cements based on calcium aluminate. By contrast with polyelectrolyte cements, these cure through hydration rather than through chelate formation or neutralization. Since these cements cure in a basic medium, without the participation of an acid, the requirements for acid resistance of the coating agent are not comparable with the requirements placed on a polyelectrolyte cement. The polymers used for surface coating in these documents are only water soluble and are also used in concentrations up to 10% as thickeners in the aqueous reaction solution which is used for hydration.
The object of the present invention is therefore to provide a polyelectrolyte cement which can be readily produced, filled into containers and mixed, and which is so stable with regard to moisture that neither its properties nor its curing are altered within the framework of normal storage conditions. If possible, this should be achieved without the need for special packaging technology and without any reduction in the mechanical values such as compression strength and bending strength.
According to the invention, this object is resolved by a single-component or multiple-component polyelectrolyte cement and/or a granulate as described in the patent claims.
Surprisingly, by contrast with the polyelectrolyte cements known from the state of the art, a surface coating of at least a part of the metal-cation-releasing compound and/or of the polyelectrolyte allows the production of a polyelectrolyte cement which is so stable in respect of atmospheric moisture that neither its curing nor properties are changed within the context of normal storage conditions; accordingly, its usefulness is not negatively influenced and the mechanical values are comparable with those of polyelectrolyte cements known from the state of the art.
Moreover, surprisingly, the tackiness of the polyelectrolyte cement to the processing instrument is reduced and the curing transition is advantageously shortened.
Characteristic of the surface coating materials according to the invention is that these are film-forming materials which are deposited onto the surface of a solid core (reactive component of the polyelectrolyte cement), which afterwards at least partially cover this core without entering into a fixed chemical bond with this core. Within the framework of the polyelectrolyte cement reaction, the surface coating agents can preferably be separated from the core, but during storage, they protect the core from the influence of moisture.
Reactive materials, which form a chemical bond with the surface of the reactive components of the polyelectrolyte cement (e.g. silanization agents as described in DE 3941629, DE 19526224 or DE 19605272) are not surface coating agents in the sense of this invention.
Film-forming materials which are already used as coating materials in the pharmaceutical industry because of their toxicological safety (see above) are preferred. Polymeric film-forming materials, in particular those with a molar mass greater than 10,000 are particularly preferred. In this context, polymers which provide an adequately high solubility in the aqueous acidic medium so that they release the reactive component sufficiently quickly and in this manner prevent the occurrence of any significant retardation of the curing reaction are particularly preferred. Preferably, the retardation should not exceed 1 minute, particularly preferably the retardation should not exceed 30 seconds.
This requirement is in contradiction to the requirement for an effective protection from moisture. Surprisingly, it was found that per se known film-forming materials, which are used for film-coated tablets in a thickness of 40-200 xcexcm, also fulfil this requirement, if they are applied to the reactive component of a polyelectrolyte cement in a concentration of less than 3%, preferably less than 2% and particularly preferably less than 1% (relative to the weight of the polyelectrolyte cement).
As a result of the large specific surface of the components, which is within the range 0.2 to 10, preferably 0.5 to 5, particularly preferably 1 to 3 m2/g, this corresponds to a film thickness of only a few nm and is therefore smaller by a factor of 1000 to 50000 than is normal in the pharmaceutical industry. To guarantee the high level of solubility, tablet coating agents which are soluble in gastric juices are preferred; polymers containing amino-functional comonomers are particularly preferred.
These polymers can be used both as such and also in a neutralized or partially neutralized form. Any acids may be used for the neutralization. However, organic acids are preferred, and carboxylic acids are particularly preferred, in particular acids which are known to be used in polyelectrolyte cements, such as hydroxycarboxylic acids, in particular, tartaric acid or citric acid.
Surprisingly, it has been shown that significantly thinner coatings than those recommended by the pharmaceutical industry for organic coating substances used in the production of tablets are sufficient to resolve the object of the invention. Even coatings in the range 0.01 to 3 wt.-%, preferably 0.1 to 2% and very particularly preferably 0.2 to 1.5 wt.-%, lead to stable systems. Within this concentration range, the materials used for the coating are not critical with reference to the other properties of the cement. The named percentage values relate to the total weight of the surface-coated material.